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GABA(A) receptor activity and PKC control inhibitory synaptogenesis in CNS tissue slices

Item Type:Article
Title:GABA(A) receptor activity and PKC control inhibitory synaptogenesis in CNS tissue slices
Creators Name:Meier, J. and Akyeli, J. and Kirischuk, S. and Grantyn, R.
Abstract:The molecular signals inducing the formation of inhibitory synapses early in development have remained enigmatic. Here we focus on the role of PKC and GABA(A)R receptor activation in the formation of GABAergic synapses in a natural cellular environment. Rapid synaptogenesis was observed in horizontal slices from the superior colliculus of embryonic (E19) rat, when GABA still acts as a depolarizing transmitter, excitatory synaptic activity is absent, and the number of already existing inhibitory synapses is very small. The vast majority of newly formed synapses expressed a GABAergic phenotype. Pharmacological block of GABA(A)R activation and Ca2+ influx through nifedipine-sensitive Ca2+ channels significantly enhanced the number of synaptic contacts, increased the immunoreactivity for GAD65, promoted synaptic accumulation of GABA(A)R clusters, and stimulated the generation of miniature IPSCs. The inhibitory synapse formation in situ was unconditionally prevented by PKC blockade and stimulated by PKC activation. Thus, a negative feedback relationship must exist between PKC and GABA(A)R activation. This new model of experimental synaptogenesis in brain slices promises to be a fruitful approach toward a better understanding of intracellular signaling cascades involved in the activity-regulated synapse formation, a problem of great clinical and theoretical relevance.
Keywords:Calcium Channel Blockers, Calcium Channels, Calcium Signaling, Cell Differentiation, Central Nervous System, Enzyme Inhibitors, Biochemical Feedback, Neural Inhibition, Organ Culture Techniques, Pregnancy, Presynaptic Terminals, Protein Kinase C, GABA-A Receptors, Superior Colliculi, gamma-Aminobutyric Acid, Animals, Rats
Source:Molecular and Cellular Neuroscience
Publisher:Academic Press
Page Range:600-613
Date:August 2003
Official Publication:https://doi.org/10.1016/S1044-7431(03)00079-4
PubMed:View item in PubMed

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